The c-myc proto-oncogene encodes a nuclear phosphoprotein which normally functions as a transcription regulatory factor and is thought to play an important role in cell proliferation and differentiation. Deregulated expression of c-myc has been associated with neoplastic transformation. Defining the regulatory mechanisms affecting c-myc expression may help to better understand the molecular mechanisms of carcinogenesis. Post- transcriptional gene regulation has been shown to be an important determinant of c-myc expression. The proposed studies are designed to define the cis-acting elements determining steady-state expression of c- myc and mediating down-regulation of c-myc expression during cellular differentiation and to define the mechanisms of regulation. Based on results of these studies, we will begin to characterize and identify the trans-regulatory factors mediating c-myc regulation. Common regulatory motifs will be sought between c-myc and other short-lived mRNAs, including those encoding other factors involved in cell proliferation and differentiation.